The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes

J Biol Chem. 2005 Oct 21;280(42):35760-6. doi: 10.1074/jbc.M508234200. Epub 2005 Aug 17.

Abstract

Combined phylogenetic and chromosomal location studies suggest that the orphan receptor RDC1 is related to CXC chemokine receptors. RDC1 provides a co-receptor function for a restricted number of human immunodeficiency virus (HIV) isolates, in particular for the CXCR4-using HIV-2 ROD strain. Here we show that CXCL12, the only known natural ligand for CXCR4, binds to and signals through RDC1. We demonstrate that RDC1 is expressed in T lymphocytes and that CXCL12-promoted chemotaxis is inhibited by an anti-RDC1 monoclonal antibody. Concomitant blockade of RDC1 and CXCR4 produced additive inhibitory effects in CXCL12-induced T cell migration. Furthermore, we provide evidence that interaction of CXCL12 with RDC1 is specific, saturable, and of high affinity (apparent KD approximately 0.4 nM). In CXCR4-negative cells expressing RDC1, CXCL12 promotes internalization of the receptor and chemotactic signals through RDC1. Collectively, our data indicate that RDC1, which we propose to rename as CXCR7, is a receptor for CXCL12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal / chemistry
  • Biotinylation
  • Cell Line
  • Cell Movement
  • Chemokine CXCL12
  • Chemokines, CXC / chemistry
  • Chemokines, CXC / physiology*
  • Chemotaxis
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Electroporation
  • Flow Cytometry
  • Genetic Vectors
  • HIV / metabolism
  • Humans
  • Kinetics
  • Ligands
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Receptors, CXCR
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, G-Protein-Coupled / physiology*
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / virology

Substances

  • ACKR3 protein, human
  • Antibodies, Monoclonal
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Ligands
  • Receptors, CXCR
  • Receptors, G-Protein-Coupled